Clinical Trial for PB-119 in Subjects With Type 2 Diabetes Mellitus

A Randomized, Open, Comparative to the Positive-Controlled, Parallel Group, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PB-119 to Subjects Newly Diagnosed as Type 2 Diabetes Mellitus

This is a randomized, opened, positive drug-controlled (Exenatide, Byetta), sequential parallel group, multiple dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of twelve once-weekly subcutaneous doses of PB-119 to subjects with type 2 diabetes mellitus (T2DM).

Study Overview

• Status: Completed
• Conditions: Type II Diabetes Mellitus
• Intervention / Treatment: Biological: PB-119 injection; Biological: Exenatide injection(Byetta)

Detailed Description

There are two study phases according to different doses of investigational drug Phase 1：1 investigational group and 1 control group, i.e.; investigational drug PB-119 injection 25µg group and control drug exenatide group.

Phase 1： Plan to have 1 or 2 investigational group according to the study result from phase 1, i.e., investigational drug PB-119 injection 50 µg group and control drug exenatide group.

Subject Number：18 subjects will be randomized to each group, with equal number of females and males. 12 subjects will be in PB-119 group, 6 subjects will be in exenatide group.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • No.1 Hospital of Peking University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and/or female subjects between the ages of 18~45 (inclusive) years, the ratio of females to males is approximately 1:1;
2. Subject has been disguised as type 2 diabetes within 5 years of screening, and met the diagnosis criteria of type 2 diabetes in guidance from WHO and Chinese Diabetes Society (CDS);
3. Subject didn't received any treatment for diabetes before screening, subject has been on diet control for more than 3 months, Fasting Plasma Glucose (FPG) was 7.0 ~ 13.0 mmol / L (including boundary value), and the glycosylated hemoglobin (HbA1c) was 7.0% ~ 10% (Including boundary values);
4. Female weight of ≥45 kg, male weight of ≥50 kg, subject body mass index (BMI) between 19~30 kg/m2 (inclusive);
5. Subject can understand the procedures and methods of this clinical trial, is willing to participate and sign the written informed consent;

Exclusion Criteria:

1. Subject was diagnosed as type 1 diabetes
2. Subject has acute complications of diabetes, such as ketoacidosis or hyperosmolar coma within 6 months before screening;
3. Subject who is allergic to exenatide, investigational drug or any ingredients (citric acid, mannitol, m-cresol); or have specific severe drug allergy history
4. Patient has specific cardiovascular disease, such as unstable angina pectoris, myocardial infarction, hypertension with poor control using one antihypertensive drugs (mean sitting systolic blood pressure ≥ 160mmHg or diastolic blood pressure ≥ 95mmHg), severe arrhythmia, QTc Prolonged, cardiac dysfunction and so on;
5. Subject who has liver and kidney dysfunction (ALT or AST> 2 times of upper limit of normal reference range, or TBIL> 1.5 times of upper limit of normal reference range, or Cr> upper limit of normal reference range);
6. Subject who's triglyceride≥5mmol/L；
7. Subject who has acute or chronic hepatitis, or other liver disease
8. Known medical history of acute pancreatitis or chronic pancreatitis, or pancreatic amylase> upper limit of normal reference range, or serum lipase> upper limit of normal reference range;
9. Subject has disease which may impact gastric emptying, such as gastroparesis, gastric outlet obstruction, intestinal obstruction, or received gastric bypass surgery, or long-term use of drugs which may have direct impact on gastrointestinal peristalsis;
10. Subject has any clinical significant major disease history or medical history of respiratory system, digestive system, nervous system, hematology system, urology system, immunology, psychiatric system and metabolic disorders etc.
11. Subject has liver, kidney or gastrointestinal partial resection surgery
12. Subject has drug abuse or alcoholic
13. Subject who has received any Chinese and western medication treatment for diabetes;
14. Subject who has taken any prescription or over-the-counter medications (such as orlistat, sibutramine, rimonabant, phenylpropanol or chlorpheniramine) that promote weight loss within 3 months before study;
15. Take any medications that may affect test results, such as antibiotics, non-steroidal anti-inflammatory drugs, antacids containing aluminum or magnesium, diuretics, anticoagulants, central nervous system inhibitors, systemic corticosteroids, medications to slow down the gastrointestinal motility, and any drug that may possibly affect the absorption of the drug within 2 weeks before screening;
16. Participated any clinical trial within 3 months before trial;
17. Female who is pregnant or lactating;
18. Subject who is not able to use contraceptive methods that is medically recognized during study;
19. Subject who cannot complete study due to other reason or determined by investigators as inappropriate to participate this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PB-119 injection; PB119 injection 25ug or 50ug once each week, for three months	Biological: PB-119 injection
ACTIVE_COMPARATOR: Exenatide Injection (Byetta); Byetta 5ug or 10ug twice each day, for three months	Biological: Exenatide injection(Byetta)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent AE (safety and tolerability)	N of participants with abnormal lab values and AE relevant to the treatment	the change form base line lab values at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PB-119 blood concentration	N of PB-119 blood concentration	hour0, hour12, hour24, hour48, hour72, hour96, hour120, hour144, hour168, hour336, hour504, hour672, hour1344, hour1848, hour1872, hour1896, hour1920, hour2016, hour2112, hour2184 and hour2580

Collaborators and Investigators

• Sponsor: PegBio Co., Ltd.
• Investigators: Principal Investigator: Yuan Lv, No.1 Hospital of Peking University

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 8, 2015
• Primary Completion (ACTUAL): September 30, 2016
• Study Completion (ACTUAL): October 27, 2016

Study Registration Dates

• First Submitted: February 15, 2017
• First Submitted That Met QC Criteria: February 16, 2017
• First Posted (ACTUAL): February 23, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 23, 2017
• Last Update Submitted That Met QC Criteria: February 16, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; pharmacodynamics
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: ICP-I-2015-01

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No