Evaluate the Pharmacokinetics of Warfarin When Coadministered With PEX168 in Healthy Adult Subjects

An Open-label,Sequential,Single-site Study to Evaluate the Pharmacokinetics of Warfarin When Coadministered With Polyethylene Glycol Loxenatide (PEX168) in Healthy Adult Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PEX168; Drug: Warfarin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male aged 18 to 45 years (including both ends) at the time of signing the informed consent.
2. Weighing not less than 50kg，Body Mass Index (BMI)of 18 to 25kg/m2. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (Tbil) are within the normal range during screening;
3. Estimated creatinine clearance (Clcr) ≥90ml / min calculated by the Cockcroft-Gault (CG) formula ;
4. Capable of giving written informed consent, which included compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

1. The hepatitis B surface antigen, hepatitis C antibody, HIV antibody test positive;
2. Having history of syncope, palpitations, bradycardia, tachycardia and other anomalies, or via a comprehensive physical examination , routine laboratory tests (blood count, blood biochemistry, urine, etc.), 12-lead ECG, abdominal B ultrasound, and other abnormalities and clinical significance persons before screening;
3. Having Alcohol and drug abuse within first 6 months before screening;
4. Smoked within 3 months before screening;
5. In screening period, blood pressure greater than 140 / 90mmHg, retest after diagnosis or pulse rate is higher than 100bpm person;
6. In screening period, ECG QTc> 450ms,diagnosed after retest;
7. Having a history of drug or allergic reactions or allergic constitution have hypersensitivity to any of the following:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Warfaring and PEX168(200µg); Warfarin: 5mg, oral Administration. PEX 168: 200µg,injected subcutaneously,once a week.	Drug: PEX168; 200µg,injected subcutaneously,once a week.; Other Names: Polyethylene Glycol Loxenatide; Drug: Warfarin; 5mg,oral,two times.; Other Names: Warfarin sodium tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events and serious adverse events	Baseline to Day78

Collaborators and Investigators

• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jianzhong Shentu, MD, The first affiliate of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): December 12, 2015
• Study Completion (Actual): July 13, 2016

Study Registration Dates

• First Submitted: May 26, 2015
• First Submitted That Met QC Criteria: May 30, 2015
• First Posted (Estimate): June 3, 2015

Study Record Updates

• Last Update Posted (Estimate): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 23, 2017
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus
• Additional Relevant MeSH Terms: Anticoagulants; Warfarin
• Other Study ID Numbers: PEX168-Ii

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO