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To assess the effect of PEX168 doses on the pharmacokinetics of warfarin in healthy subjects.To provide a scientific basis for clinical drug combination of PEX168.
To evaluated the impact of pharmacodynamics coadministrated hypodermic PEX168 and warfarin in healthy subjects.
To assess the safety of single doses of warfarin administered with and without PEX168
This was an open-label, sequential, single-center study that evaluated the pharmacokinetics of warfarin when coadministered with PEX168 in healthy adult subjects. The total duration of each subject's participation in the study was approximately 13 weeks, which included up to a 14-day Screening Period, a 51-day Treatment Period, and an approximately 4-week Follow-up Period.
Center: This study was conducted at a single site in the first affiliate hospital of Zhejiang University.All subjects receives a single 5mg oral dose of warfarin on Day 1 followed by 5 weekly 200μg doses of PEX168 injected subcutaneously beginning on Day 8 and a second single 5mg oral dose of warfarin on Day 44.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Warfaring and PEX168(200µg) | Experimental | Warfarin: 5mg, oral Administration. PEX 168: 200µg,injected subcutaneously,once a week. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PEX168 | Drug | 200µg,injected subcutaneously,once a week. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Composite measure the plasma concentrations of warfarin | Plasma concentrations of warfarin, and to calculate the pharmacokinetic parameters: Tmax、Cmax、AUC0-t、AUC0-∞、λz ,t1/2、Vd/F、CL/F etc. | Baseline to Day51 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events and serious adverse events | Baseline to Day78 |
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Inclusion Criteria:
Exclusion Criteria:
1) Warfarin and / or any of its ingredients or other similar drugs . 2) PEX168
8. Before screening, having a history of cardiovascular disease or a history of pulmonary disease ;
9. The history of thromboembolic disease or undergoing surgery or gastrointestinal bleeding within 6 months before screening, or excessive bleeding or a history of heparin-induced thrombocytopenia have significant bleeding history or family history;
10.In screening period,platelet count or international normalized ratio (INR) or activated partial thromboplastin time (APTT) greater than the upper limit of the normal range or fibrinogen is less than the lower limit of the normal range;
11. In screening period , fasting triglycerides test result was greater than the upper limit of normal range;
12. Currently there is a history of liver disease or liver disease or a known hepatobiliary abnormalities (except asymptomatic gallstones);
13. Participate in blood donation and donation amount ≥400ml within three months before screening;
14. In screening period, having thyroid dysfunction or a history;
15. The history of gastrointestinal surgery before screening;
16. The history of pancreatitis;
17. History of cholecystitis gallbladder disease or other disease history;
18. The history of inflammatory bowel disease or a history of irritable bowel syndrome;
19. The history of Type 2 multiple endocrine neoplasia;
20. The history of medullary thyroid cancer;
21. The family has type 2 multiple endocrine fibromatosis or a history of medullary thyroid cancer;
22. Three months before screening, participated in any drug or medical device trials are (including placebo);
23. Using any of the tested drugs may affect prescription drugs , non-prescription drugs, herbal (especially ginseng, oral hypoglycemic agents) or multivitamin supplements persons;
24. Drinking medication or caffeine-containing xanthine food and beverage (listed in annex 3), strenuous exercise, or other effects of drug absorption, distribution, metabolism, excretion and other factors 2 days before screening.
25. Received GLP-1 analogs (e.g. exenatide) treatment;
26. Reluctant to take an effective method of contraception during the test;
27. Researchers believe any situation that might lead to any subject cannot complete the study or to the subject of this study bring significant risk.
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| Name | Affiliation | Role |
|---|---|---|
| Jianzhong Shentu, MD | The first affiliate of Zhejiang University | Principal Investigator |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C000601947 | polyethylene glycol loxenatide |
| D014859 | Warfarin |
| ID | Term |
|---|---|
| D015110 | 4-Hydroxycoumarins |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 |
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| Warfarin | Drug | 5mg,oral,two times. |
|
|
| D004700 | Endocrine System Diseases |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |