Clinical trial NCT01475279: A Study to Evaluate the Effect of T89(Dantonic®)on Steady-State Pharmacodynamics of Warfarin
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Warfarin
Dantonic
Pharmacodynamics
Pharmacokinetics
Interaction
Lead sponsor: Tasly Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-11-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

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

Eligibility criteria: 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.

Primary outcomes:
measure: The change in INR with T89 (Day 25) compared with that without T89 (Day 18)
timeFrame: outcome measure will be assessed in two weeks and data will be presented up to eight weeks
Secondary outcomes:
measure: The change in PK variables for R-warfarin and S-warfarin on Day 17 compared with those on Day 24
timeFrame: outcome measure will be assessed in two weeks and data will be presented up to eight weeks
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Healthcare Discoveries, LLC d/b/a ICON Development Solutions
state: Texas
Study officials:
References: