Clinical trial NCT01965509: A PK/PD Study of Polyethylene Glycol Loxenatide in Patients With Type 2 Diabetes
Official title: A Double-Blind, Multicenter, Randomized Study Evaluating the Safety, and Pharmacokinetic/Pharmacodynamic Relationship in T2DMs Treated With 12 Weeks Injection of Polyethylene Glycol Loxenatide Add to Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes
Keywords: PEX168
Phase I/II
add on to metformin
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: China-Japan Friendship Hospital
First posted: 2013-10-18
Enrollment: 120
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 the effective therapeutic concentration range of PEX168, also decided to observe safety and PK/PD correlation by long-term continuous administration.


Eligibility criteria: Inclusion Criteria:

1. Has been diagnosed with type 2 diabetes mellitus.
2. Has been treated with a stable dose of metformin monotherapy ≥ 12 weeks before randomization, and metformin dose ≥ 1500 mg / day.
3. Has HbA1c of 7.5% to 11.0%(local) at screening. And has HbA1c of 7.0% to 11.0%(Central) before randomization.
4. Is 20 to 70 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 other hypoglycemic drugs (including Chinese herbal medicine) except for metformin within 3 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 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes (e.g., Cushing's syndrome or acromegaly-associated diabetes);
   * 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;
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;
   * Fasting plasma triglyceride ≥ 5.64 mmol/L (500mg/dL);
   * 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.

Primary outcomes:
measure: To assess HbA1C levels after treatment
timeFrame: 12 weeks
Secondary outcomes:
measure: To assess Fasting blood glucose levels
timeFrame: 12 weeks
Other outcomes:
measure: To assess the body weights after the treatment
timeFrame: 12 weeks
measure: To assess number of participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 12 weeks
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
Study officials:
affiliation: China-Japan Friendship Hospital
name: Wenying Yang, M.D
role: PRINCIPAL_INVESTIGATOR
References: