A Phase I Study of Polyethylene Glycol Loxenatide in Patients With Type 2 Diabetes

A Double-Blind, Multicenter, Randomized Study Evaluating the Safety, Tolerability and Pharmacokinetic/Pharmacodynamic Relationship in T2DMs Treated With 14 Weeks Injection of Polyethylene Glycol Loxenatide

Polyethylene Glycol Loxenatide (PEX168) is a new human glucagon-like peptide 1 (GLP-1) analogue that created on the basis of the Exenatide and modified by polyethylene glycol (PEG).

This study aims to evaluate whether the titration mode of administration could reduce the incidence of adverse reactions of PEX168, also decided to observe long-term continuous administration of PK/PD correlation.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Chengdu, China
    • People's Liberation Army General Hospital of Chengdu Military Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Has been diagnosed with type 2 diabetes mellitus
2. Has been treated with either: diet and exercise alone, or with a stable regimen of one or combination of two oral antihyperglycaemic agents (except TZDs), for a minimum of 3 months prior to study start.
3. Has HbA1c of 7.5% to 11.0%, inclusive.
4. Is 20 to 72 years old, inclusive.
5. Has a body mass index (BMI) of 19 kg/m2 to 35 kg/m2, inclusive.

Exclusion Criteria:

1. Skin test of PEX168 is positive.

2. Is currently treated with any of the following excluded medications:

   • GLP-1 or GLP-1 analogues prior to study start;
   • Insulin within 6 months prior to study start;
   • Growth hormone within 6 months prior to study start;
   • Abuse of drug or alcohol within 6 months prior to study start;
   • Any clinical trials of drugs or medical instruments within 3 months prior to study start;
   • Systemic corticosteroids by oral, parenteral, or intra-articular route
   • Any drugs for weight loss or operations leading to weight instable within 2 months prior to study start;
   • Any drugs that may interfere the evaluation of safety and efficiency of investigated drugs, drugs or herbals medicine that may result in toxicity to main organs prior to study start;

3. A history or evidence of any of the following :

   • Severe hypoglycemia history (e.g., sleepiness, consciousness disorder, deliration, coma led by hypoglycemia )
   • Type 1diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes (e.g., Cushing's syndrome or acromegaly-associated diabetes).
   • Other endocrine diseases (e.g., hyperthyreosis, hypothyroidism)
   • Acute or chronic gastrointestinal diseases that were not suitable for the trials evaluated by investigators.
   • Hypertension with SBP>140mmHg, and/or DBP >90mmHg after antihypertensive therapy.
   • Severe cardiovascular diseases histories including congestive heart failure (NYHA III or IV), unstable angina, stroke or TIA, myocardial infarction,sustained and clinically relevant ventricular arrhythmia, coronary artery bypass surgery or percutaneous coronary intervention.
   • Acute or chronic pancreatitis history, or pancreas injury history, or any high risk factors which may result in pancreatitis.
   • Malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, regardless of whether there is evidence of local recurrence or metastases.
   • Medullary thyroid carcinoma history, or multiple endocrine neoplasia history.
   • Acute metabolic complications such as ketoacidosis, lactic acidosis, or hyperosmolar state (coma) , or maculopathy , or instability of proliferative retinopathy within the past 6 months.
   • Weight change is over 10% within 3 months prior to the study start.
   • hepatitis B positive, hepatitis C antibody positive, HIV antibody positive, syphilis antibody positive.

4. Any of the following significant laboratory abnormalities:

   • Alanine aminotrasferase (ALT) and/or asparatate aminotransferase (AST)>2*upper limit of normal (ULN), and/or total bilirubin>1.5*ULN, confirmed by repeat measure;
   • Creatinine > upper limit of normal, confirmed by repeat measure, and/or proteinurea>++ and 24 hour urinary protein quantitative ≥1g.
   • Thyroid dysfunction unsuitable for this trial evaluated by investigator;
   • Hemodlastase > upper limit of normal, confirmed by repeat measure;
5. Male or female fertility are reluctant to take contraceptive method during the test, pregnancy or lactating women;
6. Any other situations which may result in the withdrawal of subjects or bring significant risk to subjects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEX168 100 microgram; PEX168 100 microgram qw sc. and the medication continued for 14 weeks	Drug: PEX168; A injection administered subcutaneously; Other Names: Polyethylene Glycol Loxenatide
Experimental: PEX168 200 microgram; PEX168 200 microgram qw sc. and the medication start form 100 microgram qw for 4 weeks and then increased to 200 microgram qw for the 10 weeks.	Drug: PEX168; A injection administered subcutaneously; Other Names: Polyethylene Glycol Loxenatide
Experimental: PEX168 300 microgram; PEX168 300 microgram qw sc. and the medication start form 100 microgram qw for 4 weeks and then increased to 300 microgram qw for the 10 weeks.	Drug: PEX168; A injection administered subcutaneously; Other Names: Polyethylene Glycol Loxenatide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess HbA1C levels after 14 weeks continuous treatment	14 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess Fasting blood glucose levels	14 weeks

Other Outcome Measures

Outcome Measure	Time Frame
To assess number of participants with Adverse Events as a Measure of Safety and Tolerability	14 weeks
To assess the body weights after the treatment	14 weeks

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Collaborators: People's Liberation Army General Hospital of Chengdu Military Region
• Investigators: Principal Investigator: Xiaolan Yong, M.D, People's Liberation Army General Hospital of Chengdu Military Region

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: June 12, 2013
• First Submitted That Met QC Criteria: October 15, 2013
• First Posted (Estimate): October 18, 2013

Study Record Updates

• Last Update Posted (Estimate): October 18, 2013
• Last Update Submitted That Met QC Criteria: October 15, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Phase I; PEX168; titration
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: PEX168-I-05