Healthy
Conditions
Keywords
Warfarin, Dantonic, Pharmacodynamics, Pharmacokinetics, Interaction
Brief summary
The purpose of this study is to evaluate the potential effect of Dantonic on the steady-state pharmacodynamics and pharmacokinetic of warfarin in healthy subjects and safety of the co-administration of Dantonic and warfarin.
Detailed description
Due to a large proportion of patients that could benefit from Dantonic treatment is likely to take warfarin concomitantly. And there is no systematic experience of warfarin drug-drug interaction between Dantonic and warfarin on humans. It is highly relevant to investigate the potential interaction of theses two drugs. Primary endpoint: •The change in INR with T89 (Day 25) compared with that without T89 (Day 18) Secondary endpoints: * The change in PK variables for R-warfarin and S-warfarin on Day 17 compared with those on Day 24 * Safety assessments across all time points
Interventions
DRUGWarfarin; Dantonic
Individual warfarin dose during the study; 225mg Dantonic b.i.d for one week
Sponsors
Tasly Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Nonsmoking male or female with 18-50 years of age and a body mass index (BMI) from 19.0 to 30.0 kg/m2; 2. Healthy adult with no active medical problems or significant chronic diseases as determined by the study doctor based on medical history, physical examination and laboratory evaluations; 3. Taking no medications 2 weeks before Day 0 and during the study, including drugs of abuse, prescription and non prescription medications (including natural health products, Vitamins, and herbals) and did not receive vaccinations; 4. Agree to avoid eating Seville oranges, grapefruits (including grapefruit juice), broccoli, brussels sprouts, charcoal-grilled meats, alcoholic beverages, and caffeine- and theobromine-containing beverages and foods from the time of screening visit and the duration of the study; 5. Agree to maintain adequate birth control, independent from hormonal contraceptive use, from the time of the screening visit and during the study, at the discretion of the investigator; 6. Agree to abstain from alcoholic beverages, caffeinated beverages and orange juice from 6pm the night before a study day until completion of that study day; 7. A negative fecal occult blood test (FOBT) ; 8. Agree to avoid participation in contact sports and/or other activities with significant risk of trauma injury for 7 days after each study day; 9. Subject understands and is willing, able and likely to comply with all study procedures and restrictions; 10. Subject is able to give voluntary oral and written informed consent, at the discretion of the investigator.
Exclusion criteria
1. Subjects with an elevated INR (INR\> 1.2) at screening visit; 2. No gastrointestinal bleeding history within 12 months prior to screening visit; 3. No history of endoscopically proven peptic ulcer disease; 4. Known hypersensitivity to warfarin; 5. Prosthetic heart valves, mitral stenosis, or other conditions such as recent (\<3 months) pulmonary embolism requiring anticoagulant therapy; 6. History or presence of renal and hepatic insufficiency; 7. History of hyperthyroidism; 8. History of any bleeding disorder or hypercoagulation state; 9. Surgical or medical condition liable to interfere with the absorption, metabolism or excretion of warfarin; 10. Regular intake of other medication affecting the process of coagulation or platelet aggregation (during the 2 weeks prior to screening and/or during the run-in and treatment periods); 11. Significant change in diet likely to interfere with the effects of warfarin in the 2 weeks prior to screening and/or during the run-in and treatment periods, at the discretion of the investigator; 12. History of conditions associated with hemorrhagic risk, surgery or head injury within 6 months prior to screening visit; 13. Hematological abnormalities (thrombocytopenia, clinically significant low granulocyte count, anemia, hypofibrinogenaemia, hemophilia, purpura, hemopathy with prolongation of bleeding time); 14. Blood loss/donation \>400 mL within 12 weeks prior to the screening visit and/or during the run-in and treatment periods; 15. Known to have serum hepatitis or who are carrier of the hepatitis B surface antigen (HBsAg), or hepatitis C antibody, or have a positive result to the test for HIV antigens and/or antibodies; 16. Pregnancy or lactation; 17. Participation in any other clinical trial or receipt of an investigational drug within 60 days prior to the time of the screening visit, or previous participation in this study; 18. Those subjects unable, in the opinion of the investigator, to comply fully with the trial requirements; 19. Subjects with a recent history (within 24 months prior to the screening visit) of alcoholism or known drug dependence, at the discretion of the investigator; 20. Subjects with positive urine cotinine, urine drug screen and/or alcohol breath test; 21. In the opinion of the investigator, patients with medical history or other factors which may interfere with enrollment or the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The change in INR with T89 (Day 25) compared with that without T89 (Day 18) | outcome measure will be assessed in two weeks and data will be presented up to eight weeks | The mean INR change with T89 (Day 25) and without T89 (Day 18) will be assessed by standard t test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The change in PK variables for R-warfarin and S-warfarin on Day 17 compared with those on Day 24 | outcome measure will be assessed in two weeks and data will be presented up to eight weeks | The S- and R-warfarin concentration time profiles will be listed and displayed graphically. And 90% CI of the geometric mean ratio for Cmax and AUClast of both R- and S-warfarin will be caculated. |
Countries
United States
Outcome results
None listed