The Pharmacokinetic Study of the Combination of Digoxin and Polythylene Glycol Loxenatide Injection in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetic study of the combination of digoxin and polythylene glycol loxenatide injection (PEX168) in healthy adults，and to provide scientific basis for clinical combination of PEX168 and drugs.This study is also to evaluate the safety and tolerability of mono-digoxin or digoxin plus PEX168.

Detailed Description
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This will be an open-label, single-arm, sequential, single-center clinical trial. 16 healthy males will be admitted to the clinical facility on Day -1, the day prior to the start of dosing. The subjects will be observed in clinic twice: Day -1 to 8 and Day 37 to 44. Subjects will receive a single dose of digoxin on Day 1 followed by 5 weekly subcutaneously injected doses of PEX168 and a second single dose of digoxin on Day 38. To determine the pharmacokinetic parameters of digoxin after drug administration alone and after multiple doses of PEX168, blood and urine samples will be collected after each dose of digoxin and tested by the laboratory.The subjects will be discharged on Day 8 and Day 44. Approximately 28 days after the last discharge, the subjects will be called for a post study visit.

Official Title
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An Open-label，Single-arm，Sequential，Single-center Clinical Trial of the Pharmacokinetic Study of the Combination of Digoxin and Polythylene Glycol Loxenatide Injection (PEX168) in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Digoxin
* Drug: PEX168


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males aged from 18 to 45 years Have a body weight over 50kg, have a body mass index (BMI) 19-25 kg/m^2 (both inclusive) Alanine aminotransferase<50 U/L, aspartate aminotransferase<50 U/L, alkaline phosphatase and total bilirubin <1.5x the upper limit of normal According to Cockcroft-Gault, estimated Clcr≥90ml/min Able to comprehend and willing to sign the informed consent form Exclusion Criteria: Hepatitis B surface antigen(+)， Hepatitis C virus antibody(+)，AIDS antibody（+） History of syncope, palpitations, bradycardia and tachycardia (for example any degree of atrioventricular block, left bundle branch block, right bundle branch block), or have an abnormal result of overall physical examination (vital signs, physical examination), routine laboratory assessment (hematology, biochemistry and urinalysis), 12-lead ECG and abdominal sonography (liver, gallbladder, pancreas, spleen, kidney) Have had an alcohol and substance abuse within 6 months of screening History of smoking within 3 months of screening BP>140/90 millimetres of mercury, or heart rate >100 bpm QT interval >450ms History of drug-induced allergy or of hypersensitivity for digoxin and PEX168 History of serious heart disease or lung disease Fasting triglyceride>1.5x the upper limit of normal Subjects with liver disease or have history of liver disease or abnormal liver and gallbladder conditions Donation of blood in excess of 400 mL within the 3 months of screening; or donation of blood within 1 month of screening; or received blood transfusions within 1 month of screening. Hypothyroidism Surgery of gastrointestinal tract History of pancreatitis History of cholecystitis or other gallbladder disease History of inflammatory bowel disease or irritable bowel syndrome History of MEN type 2 syndrome History of medullary thyroid carcinoma A family history of MEN type 2 syndrome and medullary thyroid carcinoma Have participated in clinical trials with drug or medical devices involved within 3 months of screening Have received any drug that may affect the study drugs within 2 weeks of screening, including prescribed drugs, over-counted drugs, Chinese traditional medicine or multivitamins History of grapefruit juice, cranberry, mango, foods and drinks of xanthine or caffeine, strenuous exercise, or any other factor affect the absorption, distribution, metabolism and excretion of the study drug within 2 days of screening Have received any glucagon-like peptide-1 mimetic compound(e.g., exenatide) Have been disagreed to use a reliable method of birth control during the study and for 6 months following the last dose of study drug History of any other condition, which in the opinion of the investigator, may prevent the subject from following and completing the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Digoxin and PEX168<br>A single dose of 0.5mg digoxin administered on Day 1 followed by 5 weekly subcutaneous injections of a single dose of 200ug PEX168, followed by a further single dose of 0.5mg digoxin on Day 38. | Drug: Digoxin<br>* Digoxin 0.5mg tablet by mouth on Day 1 and Day 38<br>* Other names: Vanoxin;Drug: PEX168<br>* PEX168 in subcutaneous injection on Day8，15，22，29 and Day 36<br>* Other names: Polythylene Glycol Loxenatide Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of pharmacokinetic (PK) parameters of digoxin with and without PEX168 in plasma and urine (cmax, t 1/2) | Maximum observed concentration in plasma(cmax); apparent terminal elimination half-life in plasma(t1/2). | Day 1 through Day 44 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability |  | Day 1 through Day 44 |