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

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

To assess the effect of PEX168 doses on the pharmacokinetics of simvastatin(as determined by simvastation acid) in healthy subjects.

To assess the safety of single doses of simvastation administered with and without PEX168

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: PEX168; Drug: Simvastatin

Detailed Description

This was an open-label, sequential, single-center study that evaluated the pharmacokinetics of simvastatin when coadministered with PEX168 in healthy adult subjects. The total duration of each subject's participation in the study was approximately 10 weeks, which included up to a 14-day Screening Period, a 34-day Treatment Period, and an approximately 4-week Follow-up Period.

Center: This study was conducted at a single site in Shanghai Mental Health Center (SMHC)of China Treatment.All subjects receives a single 40-mg oral dose of simvastatin on Day 1 followed by 5 weekly 200μg doses of PEX168 injected subcutaneously beginning on Day 3 and a second single 40-mg oral dose of simvastatin on Day 33.

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

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200122
      • Shanghai Mental Health Center (SMHC)

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:

An individual who met all of the following criteria was eligible for the study.

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.
3. No history of cardiovascular, liver, kidney, gastrointestinal, neuropsychiatric and other diseases, no history of drug allergy.
4. Capable of giving written informed consent, which included compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

1. Known for any study drug allergy (PEX168, simvastatin) or similar drug allergy (GLP-1 receptor agonists, GLP-1 analogue, statins) or allergic constitution;
2. Having Alcohol and drug abuse within first 6 months before screening;
3. Smoked within 3 months before screening;
4. Received GLP-1 receptor agonists, GLP-1 analogs, DPP-IV inhibitors, or any other similar structure drug for treatment before screening;
5. Following a thorough medical examination, clinically significant abnormalities were found;
6. In screening period, blood pressure greater than 140 / 90mmHg, retest after diagnosis or pulse rate is higher than 100bpm person;
7. In screening period, ECG QTc> 450ms, diagnosed after retest;
8. In screening period, serum creatinine or urine protein is abnormal, and were determined to be clinically significant by the investigator;
9. In screening period, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ- glutamate GGT (γ-GT), total bilirubin (Tbil) is greater than the normal range limit, and investigator determines to have clinical significance;
10. In screening period, creatine kinase (CK) exceeds the upper limit of the normal range, and judged by the investigator to be clinical significant;
11. In screening period, having thyroid dysfunction;
12. Before screening there is a history of medullary thyroid cancer;
13. Having any surgery (including the impact of gastric emptying of gastrointestinal surgery) within 6 months before screening;
14. Participate in blood donation and donation amount ≥400ml within three months before screening, or who participate in blood donation or blood transfusion within a month;
15. Using any of the tested drugs may affect prescription drugs, nonprescription drugs, herbs, food (such as grapefruit juice) or food supplements persons 2 weeks before screening;
16. 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.
17. Any clinically significant by the investigator determined that acute diseases before Screening occurred within a month too;
18. There is a history of pancreatitis or acute pancreatitis before screening;
19. Having dyslipidemia, coronary heart disease, and a history of high cholesterol before screening.
20. There are lung disease histories, history of chronic liver and gallbladder disease, cholecystitis history, history of bladder disease, a history of colon inflammation before screening.
21. Within three months before screening participated in any drug or medical device clinical trials were (including placebo);
22. Hepatitis B surface antigen, hepatitis C antibody, HIV antibody, syphilis antibody test positive;
23. Reluctant to take effective contraceptive methods of contraception. During the trial, there was family planning within six months after their spouses during the trial or the last dose (first 33 days);
24. The investigator believe that any situation that might lead to any subject cannot be completed 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: Simvastatin and PEX168(200µg); Simvastatin: 40mg, oral Administration. PEX 168: 200µg,injected subcutaneously,once a week.	Drug: PEX168; 200µg,injected subcutaneously,once a week.; Other Names: Polyethylene Glycol Loxenatide; Drug: Simvastatin; 40mg,oral,two times; Other Names: Shujiangzhi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of simvastatin and simvastatin acid.	Plasma concentrations of simvastatin and simvastatin acid, and to calculate the pharmacokinetic parameters: Tmax, Cmax, AUC0-t, AUC0-∞, λz, t1 / 2, Vd / F, CL / F, etc.	Baseline to Day34

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events and serious adverse events	Baseline to Day67

Collaborators and Investigators

• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Huafang Li, MD, Shanghai Mental Health Center (SMHC)

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2015
• Primary Completion (Actual): May 14, 2015
• Study Completion (Actual): August 11, 2015

Study Registration Dates

• First Submitted: March 25, 2015
• First Submitted That Met QC Criteria: May 14, 2015
• First Posted (Estimate): May 19, 2015

Study Record Updates

• Last Update Posted (Estimate): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 21, 2017
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: PEX168-Ik (Other Identifier: JiangsuHaosen)

Plan for Individual participant data (IPD)

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