A Study to Evaluate the Effect of T89(Dantonic®)on Steady-State Pharmacodynamics of Warfarin

Study Overview
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Brief Summary
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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
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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

Official Title
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An Open-Label, Multiple-Dose, Single-Center, Sequential, Inpatient Study to Determine the Effect of T89 on Steady-State Pharmacodynamics of Warfarin in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Warfarin; Dantonic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nonsmoking male or female with 18-50 years of age and a body mass index (BMI) from 19.0 to 30.0 kg/m2; 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; 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; 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; 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; 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; A negative fecal occult blood test (FOBT) ; Agree to avoid participation in contact sports and/or other activities with significant risk of trauma injury for 7 days after each study day; Subject understands and is willing, able and likely to comply with all study procedures and restrictions; Subject is able to give voluntary oral and written informed consent, at the discretion of the investigator. Exclusion Criteria: Subjects with an elevated INR (INR> 1.2) at screening visit; No gastrointestinal bleeding history within 12 months prior to screening visit; No history of endoscopically proven peptic ulcer disease; Known hypersensitivity to warfarin; Prosthetic heart valves, mitral stenosis, or other conditions such as recent (<3 months) pulmonary embolism requiring anticoagulant therapy; History or presence of renal and hepatic insufficiency; History of hyperthyroidism; History of any bleeding disorder or hypercoagulation state; Surgical or medical condition liable to interfere with the absorption, metabolism or excretion of warfarin; 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); 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; History of conditions associated with hemorrhagic risk, surgery or head injury within 6 months prior to screening visit; Hematological abnormalities (thrombocytopenia, clinically significant low granulocyte count, anemia, hypofibrinogenaemia, hemophilia, purpura, hemopathy with prolongation of bleeding time); Blood loss/donation >400 mL within 12 weeks prior to the screening visit and/or during the run-in and treatment periods; 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; Pregnancy or lactation; 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; Those subjects unable, in the opinion of the investigator, to comply fully with the trial requirements; 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; Subjects with positive urine cotinine, urine drug screen and/or alcohol breath test; In the opinion of the investigator, patients with medical history or other factors which may interfere with enrollment or the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Warfarin; Dantonic|Individual warfarin dose during the study; 225mg Dantonic b.i.d for one week|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in INR with T89 (Day 25) compared with that without T89 (Day 18) | The mean INR change with T89 (Day 25) and without T89 (Day 18) will be assessed by standard t test. | outcome measure will be assessed in two weeks and data will be presented up to eight weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in PK variables for R-warfarin and S-warfarin on Day 17 compared with those on Day 24 | 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. | outcome measure will be assessed in two weeks and data will be presented up to eight weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Warfarin, Dantonic, Pharmacodynamics, Pharmacokinetics, Interaction